Spectral properties and supramolecular inclusion complex formation between 2-styrylbenzothiazolium dye and cyclodextrins

The effect of native and randomly methylated β-CDs on the absorption and steady-state fluorescence spectra of 2-(4-dimethylaminostyryl)-3-(2-hydroxyethyl)-benzothiazolium chloride (DHB) in aqueous buffer solutions with various pH values was studied. The inclusion with both CDs at pH 7.2 barely changed the UV spectra, whereas significant variations were produced in the emission spectra in all buffer solutions. In all cases the CDs increase guest fluorescence. The 1:1 stoichiometry of the inclusion complexes of the dye with both CDs was established according to the modified Benesi-Hildebrand method. Binding constant values were calculated using the iterative nonlinear least-squares regression approach. The pH of the solution and the type of the CD affected complex stability. The results indicate that native β-CD possesses better complexing ability towards DHB than randomly substituted β-CD and that the most stable inclusion complexes are formed in basic medium because of the structural changes in the guest molecule. In basic medium an attempt is made to interpret the proposed mechanism in terms of molecular rearrangement which take place as the dye penetrates the CD cavity.     

Conformation of permethylated cyclodextrins and the host-guest geometry of their inclusion complexes

Macrocylic conformation of permethylated cyclodextrins and the geometry of their inclusion complexes were examined on the basis of the X-ray data of three permethylated -cyclodextrin complexes and two permethylated -cyclodextrin complexes. The host macrocyclic ring is remarkably distorted owing to steric hindrance involving the methyl groups and the inability to form intramolecular hydrogen bonds. The guest molecules are included within the host cavity, but their position and orientation are quite different from those found in the corresponding cyclodextrin complexes.     

Cyclodextrin Inclusion Compounds in Research and Industry

α-, β-, and γ-Cyclodextrins are cyclic oligosaccharides consisting of six, seven, or eight glucose units, which can be obtained on a large scale from starch. They form inclusion compounds with smaller molecules which fit into their 5—8 Å cavity. These (crystalline) complexes are of interest for scientific research as, contrary to the classical clathrates, they exist in aqueous solution and can be used to study the hydrophobic interactions which are so important in biological systems. Cyclodextrins also serve as models both for polymeric starch and, in the form of their polyiodide complexes, for “blue iodine-starch”. As cyclodextrins catalyze several chemical reactions they and their functionalized derivatives provide useful enzyme models. Cyclodextrins can be used to advantage in the production of pharmaceuticals, pesticides, foodstuffs, and toilet articles—the (micro-encapsulated) active and aromatic substances enclosed within them are protected from the effects of light and atmosphere and can be easily handled and stored in powder from. Substances which are not very soluble in water become more soluble in the presence of cyclodextrins—creams and emulsions can be stabilized, and the growth and yield of grain harvests can be increased. Cyclodextrins can be chemically modified for many different purposes; polymerized cyclodextrin or cyclodextrin bound to a polymer carrier have already been employed in gel inclusion and affinity chromatography.     

Liquid chromatography of cyclodextrins with indirect photometric detection of phenolphthalein inclusion complexes

Summary - and -cyclodextrin (CD) separated by liquid chromatography have been indirectly detected by depression of the background absorbance at a visible wavelength by means of inclusion complexation with phenolphthalein. The background signal was generated by phenolphthalein in an alkaline medium. Octadecyl-bonded poly(vinylalcohol) packings were employed as the stationary phase, which allowed the use of alkaline mobile phases, and eliminated post column mixing of reagents. The detection limits for - and -CD were 0.1–0.5 M at a signal to noise ratio of 3. -CD could not be measured by the present detection principle.     

Determination of association constants of inclusion complexes of steroid hormones and cyclodextrins from their electrophoretic mobility

CE estimation of the association constants of several steroid hormones with beta-CD and gamma-CD and their hydroxypropyl derivative is presented. Estriol, 17beta-estradiol, ethynylestradiol, estrone, progesterone, mestranol and norethindrone are among the target analytes. The calculation of the cyclodextrin:analyte association constants were performed from the electrophoretic mobility values of steroids at different concentration of CDs in the run buffer. The reliability of the final data was ensured by employing three different linearisation plots (double reciprocal fit, Y-reciprocal fit and X-reciprocal fit). The highest inclusion affinity of target analytes was observed towards gamma-CD and its hydroxypropyl derivative, which is demonstrated by high association constant values and corresponding good linearity of the plots. The affinity of steroids towards a particular CD type based on physical and structural characteristics is explored.     

Spectroscopic study and antioxidant properties of the inclusion complexes of rosmarinic acid with natural and derivative cyclodextrins

Measurement of total antioxidant activity/capacity of polyphenols in various solvent media necessitates the use of cyclodextrins to solubilize lipophilic antioxidants of poor aqueous solubility. The inclusion complexes of the slightly water soluble antioxidant, rosmarinic acid (RA), with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), 2-hydroxyethyl-β-cyclodextrin (HE-β-CD), and methyl-β-cyclodextrin (M-β-CD) were investigated for the first time. The effect of cyclodextrins (CDs) on the spectral features of RA was measured in aqueous medium using UV-vis and steady-state fluorescence techniques by varying the concentrations of CDs. The molar stoichiometry of RA-CD inclusion complexes was verified as 1:1, and the formation constants of the complexes were determined from Benesi-Hildebrand equation using fluorescence spectroscopic data. Among the CDs, maximum inclusion ability was measured in the case of M-β-CD followed by HP-β-CD, HE-β-CD, β-CD and α-CD. Solid inclusion complexes were prepared by freeze drying, and their functional groups were analyzed by IR spectroscopy. Antioxidant capacity of CD-complexed rosmarinic acid was measured to be higher than that of the lone hydroxycinnamic acid by the CUPric Reducing Antioxidant Capacity (CUPRAC) method. The mechanism of the TAC increase was interpreted as the stabilization of the 1-e oxidized o-catechol moiety of RA by enhanced intramolecular H-bonding in a hydrophobic environment provided by CDs, mostly by M-β-CD.     

Synthesis and structural aspects of urea/dialkylamine inclusion compounds

The synthesis and structural aspects of urea host-guest inclusion compounds containing linear secondary alkylamines (dibutyl-,dipentyl-, dihexyl-, dioctyl-) at 25°C are reported. Elemental analysis,¹³C CP-MAS NMR and¹H-NMR Spectroscopy, and Powder X-ray Diffraction Analysis confirm the inclusion process. The basic host structure of the products is similar to that of urea-hydrocarbon systems.¹³C MAS-NMR experiments show chemical shift differences for the confined guest molecule with respect to the liquid phase. Stoichiometry and |c _g| values for the inclusion compounds with dipentyl-and dihexylamine suggest a commensurate structure.     

Structural studies on supramolecular adducts of cyclodextrins with the complex [Ru([9]aneS3)(bpy)Cl]Cl

The complex [Ru([9]aneS₃)(bpy)Cl]Cl (bpy = 2,2′-bipyridine) was immobilised in plain β-cyclodextrin (β-CD) and permethylated β-CD (TRIMEB) to yield two adducts with a 1:1 host:guest stoichiometry. The adducts were studied by powder X-ray diffraction (XRD), thermogravimetric analysis (TGA), ¹³C{¹H} CP/MAS NMR and vibrational spectroscopy (FT-IR and Raman). Results support the formation of stable supramolecular adducts with a proposed geometry in which the coordinated bypiridine fragment of the guest is partially included in the host cavities, and the bulky [9]aneS₃ fragment protrudes out to the interstitial spaces. A packing mode is proposed for [Ru([9]aneS₃)(bpy)Cl]Cl · TRIMEB, obtained by Monte Carlo optimisation of the XRD data. TRIMEB molecules are stacked in tilted channels, with the voluminous part of the guest molecules in the inter-channel space. The behaviour of [Ru([9]aneS₃])(bpy)Cl]Cl upon CD encapsulation and the chloride ligand hydrolysis process in solution for all compounds were studied in detail by Raman spectroscopy.     

Mebendazole complexes with various cyclodextrins: preparation and physicochemical characterization

Mebendazole is an antihelmintic drug, active against many intestinal parasites. Its systemic efficacy is limited by its poor water solubility. The use of natural or derivatized cyclodextrins permeated to multiply notably its apparent solubility, especially with permethyl β-cyclodextrine (PM β-CD) (multiplied by 4700). The inclusion complex formation between mebendazole and this methylated β-cyclodextrin, was characterized by mass spectrometry, powder X-ray diffractometry and Fourier transform infrared spectroscopy: mebendazole seemed to be included in permethyl β-cyclodextrin by its aromatic rings. To prepare inclusion complex of mebendazole and PMβ-CD by solvent evaporation, acetone may be used and the ratio using lower amount of cyclodextrin (MBZ:CD, 1:2) should be used.     

Studies on the behaviour of α-, β- and γ-cyclodextrins and some derivatives under reversed-phase liquid Chromatographic conditions

The separation processes of α-, β- and γ-cyclodextrins and their various methyl derivatives have been investigated with Knauer polarimetric (Chiralyser) and refractive index (RI) detectors. RP18 and RP8 hydrocarbon packings and an NH₂ bonded phase were applied as stationary phases. Aqueous methanolic or ethanolic solutions were used as mobile phases. It has been found that the Chiralyser detector response is approximately linear at low concentrations of solutes and that its detection capabilities are about 40 times better than those of the RI detector. Differences in the order of elution of α-, β- and γ-cyclodextrins have been observed for various stationary phases as well as for various mobile phase compositions. The optimal conditions for analytical determinations of cyclodextrins and their derivatives have been discussed.     

Capillary electrophoretic analysis of cyclodextrins with dynamic fluorescence labeling and detection

The use of 8-anilinonaphthalene-1-sulfonic acid (8,1-ANS) as buffer additive in the capillary electrophoretic separation of cyclodextrins (CDs) was investigated. Better detection sensitivity was obtained for - and γ-CDs than with previously reported capillary electrophoretic methods. Increasing the concentration of 8,1-ANS improved resolution and sensitivities for -, β- and γ-CDs, while decreasing the pH of the background electrolyte can improve sensitivities. Detection limits for -, β- and γ-CDs were determined to be 60, 20 and 7 μM, respectively. The formation constants of CD–8,1-ANS complexes at pH 6 were also measured by capillary electrophoresis. Finally the specificity of amyloglucosidase to CDs was analyzed as a practical application of this method.     

Thermal analysis of thione compounds

The thermal behavior of thiourea (Tu), N-methylthiourea (MeTu), N, N-dimethylthiourea (Me₂Tu) and N, N, N, N-tetramethylthiourea (Me₄Tu) was investigated by means of conventional thermal analysis in O₂ and N₂ and IR spectroscopy of the residues on heating in air at various temperatures.At ordinary pressure, the compounds are thermally stable up to the melting points. After melting, they show high vapor pressure, combustion in O₂ atmosphere and isomerization to ammonium thiocyanate, with the exception of Me₄Tu.Financially supported by the Italian MURST.     

Crystalline inclusion compounds of tetrabenzo-18-crown-6 with uncharged organic molecules. Solid-state structure of the nitroethane complex

Tetrabenzo-18-crown-6 (1) shows distinct solid-state inclusion properties towards a number of OH-acidic, CH-acidic and low-polar uncharged organic molecules. The single crystal X-ray analysis of the inclusion complex between1 and EtNO₂ (11) is reported. Crystals are monoclinic,P2₁/c, witha=12.887(1),b=19.365(2),c=10.776(1) Å, =96.33(2)^o,D _c=1.321g cm^–1,Z=4. The host macroring has a conformation similar to a dentist's-chair. The complex is stabilized mainly by C–H...O type interactions involving the methyl group of the EtNO₂ guest molecule which is highly disordered. The nitroethane guests are trapped in channels formed by the host macrocycles. Supplementary Data relating to this article are deposited with the British Library as Supplementary Publication No. SUP 82150 (11 pages)     

Thermal analysis of hydrazinium metal sulphates and their hydrazinates

Thermal analysis of hydrazinium metal sulphates, (N₂H₅)₂ M(SO₄)-I, and their hydrazinates, (N₂H₅)₂−M(SO₄)₂3N₂H₄−II, whereM=Fe, Co and Ni have been investigated using thermogravimetry and differential thermal analysis. Type II compounds on heating decompose through an intermediate I and metal suphlate to the respective metal oxides.     

Effect of cyclodextrins on the electrochemical behaviour of ascorbic acid on platinum electrodes in acidic and neutral solutions

The effect of β-CD and α-CD on the electrochemical behaviour of H₂A and HA⁻ on platinum is studied. The adsorption of β-CD on this electrode is demonstrated and proved to be dependent on the base electrolyte composition. The maximum adsorption coverage was reached in phosphate solution at pH 6.95. The homogeneous H₂A---β-CD complex formation produced a decrease in the oxidation current and a positive shift in the oxidation peak potential. These effects are predominant in acid solutions. In neutral solutions the opposite behaviour is observed, i.e. an increase in the oxidation current at lower oxidation potentials. The presence of a parallel oxidation route for the vitamin involving strongly adsorbed CO residues is considered, and evidence for a decrease in CO_ad in the presence of β-CD was given by variations in hydrogen adsorption charges. This fact, more important in neutral solutions, must be responsible for the catalytic effect observed. α-CD was not adsorbed, neither did it modify the electro-oxidation behaviour of H₂A and HA⁻.     

Formation of isolated guest dimers vs. host-guest coordination. X-Ray crystal structures of four carboxylic acid inclusion compounds formed by roof-shaped and scissor-like host molecules

The crystal structures of the inclusion compounds oftrans-9,10-dihydro-9,10-ethano-anthracene-11,12-dicarboxylic acid host (1) with formic acid (1a), acetic acid (1b), and propionic acid (1c) as guests, and of the coordinatoclathrate of the 1,1-binaphthyl-2,2-dicarboxylic acid host (2) with acetic acid as guest (2b) have been studied by single crystal X-ray diffraction. These studies show that inclusion of small carboxylic acids by carboxylic acid hosts like1 and2 results in formation of isolated, hydrogen-bonded guest dimers. Additional H-bond contacts between host and guest carboxylic groups are only formed in cases1a and2b. The dimeric acidic guest units are sitting in the cavities of the host or host-guest framework and have no other interactions than those of a weak Van der Waals' type with the neighbouring molecules. Crystal data:1·formic acid (1:2): triclinic (P),a = 11.6769(6),b = 9.4067(4),c = 9.0020(4) Å,a = 81.522(4), = 100.310(6), = 104.208(6)°,Z = 2,R = 0.048 for 2392 reflections;1·acetic acid (1:1): monoclinic (P2₁/n),a = 9.717(2),b = 14.462(2),c = 13.038(3)Å, = 104.27(1)°,Z=4,R=0.046 for 3042 observations;1·propionic acid (1:1): monoclinic (P2₁/n),a = 9.897(4),b = 14.671(7),c = 13.284(7) Å, = 105.92(6)°,Z = 4,R = 0.056 for 2302 reflections;2·acetic acid (2:3): triclinic (P),a = 12.746(1),b = 17.781(2),c = 11.010(1) Å, = 105.606(4), = 112.992(8), = 81.175(6)°,Z = 2,R = 0.067 for 4375 observations.     

Study on the inclusion behavior and solid inclusion complex of 5-amino-6-methyl-2-benzimidazolone with cyclodextrins

The inclusion behaviors of three native or modified CDs including p-CD,2-hydroxypropyl-β-CD(2-Hp-β-CD) and 2,6-dimethyl-β-CD(Me-β-CD) toward 5-amino-6-methyl-2-benzimidazolone(AMBI) were comparatively investigated by NMR and fluorescence titration in combination with IR spectra,X-ray diffractometry and scanning electron microphotographs.The experimental results jointly demonstrated that the phenyl ring of AMBI entered into the cavity of the CDs and located close to the narrow rims accompanied by the formation of the 1:1 inclusion complex with large stability constant in aqueous solution.The introduction of the hydroxypropyl unit to the host improved the solubility,ultimately effecting an obvious promoting in the fluorescence intensity and the stability constant     

Changes in the reactivity of the fluorescent reagents carbazole-9-carbonyl chloride and 9-carbazolylacetic acid in the presence of cyclodextrins

Carbazole-9-carbonyl chloride (C9CC) and 9-carbazolylacetic acid (9CAA) were selected as model fluorescent reagents. The effect of different chemically modified cyclodextrins (CDs) added to the aqueous solutions of these reagents was studied in water and in buffered aqueous solutions at pH 4.5 and 8.8. The CDs employed were 2-hydroxypropyl-β-cyclodextrin (HP-βCD), 2,3-di-O-methyl-β-cyclodextrin (DM-βCD) and 2,3,6-tri-O-methyl-β-cyclodextrin (TM-βCD). The inclusion of these reagents inside the cavities of the CDs was verified and this process can affect the derivatization reaction because CDs can modify the reactivity of the guest molecules. The basic conditions necessary for the derivatization reaction between C9CC and amines lead to the formation of carbazole anion through hydrolysis followed by decarboxylation. In the presence of CDs, the hydrolysis-decarboxylation of carbazole-9-carbonyl chloride is faster than in buffered aqueous homogeneous solutions. The behaviour observed for these reagents in aqueous solutions of CDs was compared to the one observed in basic ethanolic solutions. These changes are particularly noticeable in the case of 2,3-di-O-methyl-β-CD and 2-hydroxypropyl-β-CD. The characteristics of the fluorescent reagents are compared to carbazole and 9-methylcarbazole as model compounds. This paper was presented at XIIIth International Cyclodextrin Symposium. Torino, Italy, May 14–17, 2006.